HMPA Research Articles

Relationship of the solvation enthalpies of n-alkanes in a methanol–hexamethylphosphortriamide mixture to its thermal and bulk properties

Enthalpies of dissolution are determined thermochemically under standard conditions, and the solvation enthalpies of n-hexane, n-decane, and n-hexadecane in a mixed methanol–hexamethylphosphor-triamide (HMPT) solvent are calculated. Experimental data are compared to values obtained from model calculations. It is shown that positive deviations of the enthalpies of dissolution of alkanes in a МеОН–HMPT mixture from additivity in the range enriched with methanol are due to changes in the bulk properties of the mixed solvent, while negative deviations of enthalpies of dissolution from additivity in the range enriched with HMPT are due to the selective solvation of alkanes by HMPT.

Modular Total Syntheses of the Alkaloids Discoipyrroles A and B, Potent Inhibitors of the DDR2 Signaling Pathway.

The title natural product 1 has been synthesized by treating the 1,2,3,5-tetrasubstituted pyrrole 23 with oxoperoxymolybdenum(pyridine) (hexamethylphosphoric triamide) (MoOPH). Compound 23 was itself prepared in seven steps from parent pyrrole using Ullmann-Goldberg and Suzuki-Miyaura cross-coupling, Vilsmeier-Haack formylation, electrophilic bromination, and Wittig olefination reactions as key steps. Related chemistry has been used to prepare discoipyrrole B (2).

Synthesis of SiCl4 from Gaseous HCl and Si(OMe)4. Reaction Development and Kinetic Studies

This report describes a method to synthesize SiCl4 from alkyl orthosilicates and gaseous HCl. Reacting tetramethyl orthosilicate with HCl gas at 0 °C in the presence of a catalytic amount of hexamethyl phosphoramide (10 mol %) and four equivalents of acetonitrile afforded an 86% yield of SiCl4 after 6 h. Exchange between HCl and alkoxy groups on silicon during the reaction generates methanol. The methanol then reacts with acetonitrile (in the presence of HCl) to form an imidate, thus removing it from the reaction mixture. Other Lewis acid and base catalysts were also observed to accelerate the reaction. A kinetics experiment using 29Si NMR to monitor reaction intermediates in situ was conducted to determine the rates of chloride/alkoxide exchange on silicon.

Computational Studies on the Reaction from Silyl 1,4‐Dilithio 1,3‐butadiene to Lithio Silole

The reaction mechanisms forming lithio silole, 2, from silyl 1,4‐dilithio 1,3‐butadiene, 1, were examined theoretically at the CCSD/6‐31+G(d)//B3LYP/6‐31+G(d) level of theory in the gas phase. To account for the solvent effects, the reactions in diethyl ether were examined using the polarizable continuum model of the integral equation formalism (IEFPCM) with the united atom topological (UA0) cavity model at the IEFPCM‐CCSD/6‐31+G(d)//IEFPCM‐B3LYP/6‐31+G(d) level of theory. Without hexamethyl‐phosphoramide (HMPA) as a cosolvent, the lithio silole, 2, was not produced due to the higher activation barrier, which is comparable to the homolytic cleavage of CC and/or CS bonds. On the other hand, the reaction could be feasible if HMPA solvates strongly or dissociates two Li+ cations from the reaction system. This suggests that HMPA plays a decisive role in the reaction. The optimized structures of the stationary point species on the potential energy surfaces in diethyl ether were similar to those in the gas phase, suggesting that the solvent effects on the structures of stationary species were not so large. On the other hand, the values in diethyl ether showed larger changes from the corresponding values in the gas phase.

Lithium Bromide/Water as Additives in Dearomatizing Samarium-Ketyl (Hetero)Arene Cyclizations.

New conditions for dearomatizing samarium-ketyl (hetero)arene cyclizations are reported. In many examples of these samarium diiodide-mediated reactions, lithium bromide and water can be used as additives instead of the carcinogenic and mutagenic hexamethylphosphoramide (HMPA). The best results were obtained for the cyclizations of N-acylated indole derivatives delivering the expected indolines in good yields and excellent diastereoselectivities. A new type of cyclization delivering indolyl-substituted allene derivatives is also described. The scope and limitations of the lithium bromide/water system are discussed.

Enhanced plasmid DNA utilization in transiently transfected CHO-DG44 cells in the presence of polar solvents.

Although the protein yields from transient gene expression (TGE) with Chinese hamster ovary (CHO) cells have recently improved, the amount of plasmid DNA (pDNA) needed for transfection remains relatively high. We describe a strategy to reduce the pDNA amount by transfecting CHO-DG44 cells with 0.06 μg pDNA/10(6) cells (10% of the optimal amount) in the presence of nonspecific (filler) DNA and various polar solvents including dimethylsufoxide, dimethyl formamide, acetonitrile, dimethyl acetamide (DMA), and hexamethyl phosphoramide (HMP). All of the polar solvents with the exception of HMP increased the production of a recombinant antibody in comparison to the untreated control transfection. In the presence of 0.25% DMA, the antibody yield in a 7-day batch culture was 500 mg/L. This was fourfold higher than the yield from the untreated control transfection. Mechanistic studies revealed that the polar solvents did not affect polyethylenimine-mediated pDNA delivery into cells or nuclei. The steady-state transgene mRNA level was elevated in the presence of each of the polar solvents tested, while the transgene mRNA half-life remained the same. These results indicated that the polar solvents enhanced transgene transcription. When screening a panel of recombinant antibodies and Fc-fusion proteins for production in the presence of the polar solvents, the highest increase in yield was observed following DMA addition for 11 of the 12 proteins. These results are expected to enhance the applicability of high-yielding TGE processes with CHO-DG44 cells by decreasing the amount of pDNA required for transfection.

Lewis acid-induced change from four- to two-electron reduction of dioxygen catalyzed by copper complexes using scandium triflate.

Mononuclear copper complexes, [(tmpa)Cu(II)(CH3CN)](ClO4)2 (1, tmpa = tris(2-pyridylmethyl)amine) and [(BzQ)Cu(II)(H2O)2](ClO4)2 (2, BzQ = bis(2-quinolinylmethyl)benzylamine)], act as efficient catalysts for the selective two-electron reduction of O2 by ferrocene derivatives in the presence of scandium triflate (Sc(OTf)3) in acetone, whereas 1 catalyzes the four-electron reduction of O2 by the same reductant in the presence of Brønsted acids such as triflic acid. Following formation of the peroxo-bridged dicopper(II) complex [(tmpa)Cu(II)(O2)Cu(II)(tmpa)](2+), the two-electron reduced product of O2 with Sc(3+) is observed to be scandium peroxide ([Sc(III)(O2(2-))](+)). In the presence of 3 equiv of hexamethylphosphoric triamide (HMPA), [Sc(III)(O2(2-))](+) was oxidized by [Fe(bpy)3](3+) (bpy = 2,2-bipyridine) to the known superoxide species [(HMPA)3Sc(III)(O2(•-))](2+) as detected by EPR spectroscopy. A kinetic study revealed that the rate-determining step of the catalytic cycle for the two-electron reduction of O2 with 1 is electron transfer from Fc* to 1 to give a cuprous complex which is highly reactive toward O2, whereas the rate-determining step with 2 is changed to the reaction of the cuprous complex with O2 following electron transfer from ferrocene derivatives to 2. The explanation for the change in catalytic O2-reaction stoichiometry from four-electron with Brønsted acids to two-electron reduction in the presence of Sc(3+) and also for the change in the rate-determining step is clarified based on a kinetics interrogation of the overall catalytic cycle as well as each step of the catalytic cycle with study of the observed effects of Sc(3+) on copper-oxygen intermediates.

Phosphine-mediated addition of 1,2-dicarbonyls to diazenes: an umpolung approach toward N-acyl hydrazone synthesis

Using a Kukhtin–Ramirez-like condensation employing hexamethylphosphorous triamide, the addition of 1,2-dicarbonyls to diazenes affords direct access to N-acyl hydrazones in moderate to excellent yields. The strategic assembly of this ubiquitous functional group proceeds through an umpolung disconnect in which an in situ generated acyl anion equivalent reacts with an electrophilic azodicarboxylate to form a new C–N bond. The method presented herein complements traditional condensation approaches toward hydrazone synthesis to access important synthetic intermediates and potentially biologically relevant architectures.

A Convenient Synthesis of 1,3,2-Benzodiazaphophorine-2-oxide

The reaction of amidines 1 with hexamethylphosphoric triamide in refluxing toluene is described as a simple and efficient method for the synthesis of 1,3,2-diazaphosphorine-2-oxide derivatives 3. The structures of all the synthesized compounds have been established by NMR (1H, 13C, 31P) and IR spectroscopy, as well as by elemental analysis and in the case of 3d by MS spectral data.

Stereoselective reactions of a thioester butanediacetal with various electrophiles

The reactions of the lithium enolate of S-ethyl (2R,5R,6R)-5,6-dimethoxy-5,6-dimethyl-[1,4]-dioxane-2-carbothioate were investigated in the presence or absence of hexamethylphosphoramide (HMPA). Fluorination gave a single isomer with a much better yield than for the corresponding methyl ester. Alkylation with alkyl halides strongly depended upon their structure. Without HMPA, only methyl iodide reacted with moderate yield and gave a single isomer. In the presence of HMPA, all of the alkyl halides reacted almost quantitatively (81–98% yield) with moderate stereoselectivity and preferentially gave products with the alkyl chain attached at the equatorial position. The silyl enol ether obtained from the thioester had the opposite geometry to that obtained from the methyl ester, which thus explains the difference in stereoselectivity between these two compounds.

The redox potential of the phenyl radical/anion couple and the effect thereon of the lithium cation: A computational study

The most popular E0Ph/Ph− value is incorrect and cannot actually be obtained from the up-to-date experimental electrochemical data only. Quantum chemical calculations presented in this work showed that the accurate E0Ph/Ph− values are equal to −1.28, −1.27 and −1.84V vs. Fc+/Fc, in MeCN, DMF and THF, respectively. These were based on the reference gas-phase electron affinity for phenyl radical from the explicitly correlated coupled-cluster method (CC) and the SMD solvation free energies of Ph/Ph− at the DFT level. The differences between CC-based and purely DFT redox potentials were below 0.1V. Using a solvation model with a mixed implicit/partially explicit treatment of the coordinating solvent allowed the calculation (at the DFT level) of the standard oxidation potential of phenyllithium in THF, −0.93V vs. Fc+/Fc, which reflects a strong effect of Li+. The substitution of just one explicit molecule of ether solvent by hexamethylphosphoramide (HMPA) shifts this potential cathodically by 0.13V.

Reactivity of mixed organozinc and mixed organocopper reagents: 11. Nickel‐catalyzed atom‐economic aryl–allyl coupling of mixed (n‐alkyl)(aryl)zincs

Group selectivity in the allylation of mixed (n‐butyl)(phenyl)zinc reagent can be controlled by changing reaction parameters. CuCN‐catalyzed allylation in tetrahydrofuran (THF)–hexamethylphosphoric triamide is n‐butyl selective and also γ‐selective in the presence of MgCl2, whereas CuI‐catalyzed allylation in THF in the presence of n‐Bu3P takes place with a n‐butyl transfer:phenyl transfer ratio of 23:77 and an α:γ transfer ratio of phenyl of 76:24. NiCl2(Ph3P)2‐catalyzed allylation in the presence of LiCl is phenyl selective with an α:γ ratio of 65:35. The reaction of methyl‐ or n‐butyl(aryl)zinc reagents with an allylic electrophile in THF at room temperature in the presence of NiCl2(Ph3P)2 catalyst and LiCl as an additive provides an atom‐economic alternative to aryl–allyl coupling using diarylzincs. Copyright © 2014 John Wiley & Sons, Ltd.

Preparation and Structure of Double Complex Compounds [La(HMPA)4(NO3)2][Cr(NH3)2(NCS)4

This paper presents the results of chemical analysis, IR- spectroscopic analysis, thermal gravitational analysis, X-ray phase analysis, and X-ray structural analysis, conducted to determine the composition, structure and properties of the double complex salts - tetra(isotiocyanato)diaminechromates(III) of complex lanthanon(III) of ceric group with hexamethylphosphorotriamide (HMPA) and nitrate-groups as ligands.

Heterogeneous Oxidation of Sulfides by Hexamethylphosphoramide/Polyoxometalate Hybrid Catalysts

In this research, � -H4PW12O40 heteropoly acid (HPAs) is used as building blocks for designation functional materials novel organic–inorganic hybrid polyoxometalate (POM), H4PW12O40 · nHMPA, with hexamethylphosphoramide (HMPA) as the organic ligand. Different host-guest systems are then designed based on the prepared hybride POM using mesoporous silicas with different textural properties as hosts. MCM-48 and SBA-15 mesoporous silicas are synthesized hydrothermally and SBA3 is produced via sol–gel method. MCM-48 and SBA-15 are then functionalized with aminopropyl functional groups via grafting method. The parent Keggin HPA is also intercalated within SBA-15, as a model for other supports, to perform closer and more efficient investigation. The mesostructured organic–inorganic hybrid materials are characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), Transmition Electron Microscopy (TEM), Atomic absorption, BET-BJH, and CHN elemental analysis. Effects of physical (texture) and chemical (functional groups) properties of the immobilizing supports on immobilization pattern and quality are then taken into consideration. The newly designed hybrid catalysts are investigated for heterogeneous oxidation of sulfides. Reaction conditions are optimized by finding the most proper temperature, solvent, and catalyst amount. An interpretation of the differences in the catalytic activity of the precursors is put forward and their catalytic activity is compared with their HPA counterparts. Furthermore, effects of support texture, pore structure, and functionalities on catalyst activity, stability, and reusability are clarified. Tests are also performed to assure the heterogeneous nature of the systems. Results reveal that the designed mesostructured hybrid POM catalysts can selectively oxidize sulfides in presence of hydrogen peroxide as oxidant. The catalysts are shown to be heterogeneous and reusable without significant loss of activity in the proceeding rounds. Such kind of materials can be actively used as environmentally benign, green, and selective heterogeneous catalysts for oxidation of sulfides.

ChemInform Abstract: Interaction of Hexamethylphosphoric Triamide with m‐Dinitrobenzenes.

Heating of 1-X-3,5-dinitrobenzenes (X is an electron-withdrawing group) in hexamethylphosphoric triamide affords the corresponding 1-X-3-dimethylamino-5-nitrobenzenes.

Simultaneous determination of phosphorous by-products and inorganic anions in glyphosate mother liquor by ion chromatography with suppressed-conductivity detection

The by-product anion content was an important index for the evaluation of pesticide glyphosate's productivity technology. A method was developed for the simultaneous determination of glyphosate, phosphorous by-products and other trace impurity anions in the mother liquor of glyphosate procedure by ion chromatography (IC). The sample was diluted with deionized water and filtrated by 0.22 microm nylon filter membrane, and then analyzed by IC directly without anymore pretreatment. The analytical column was Dionex IonPac AS11-HC (250 mm x 4 mm) with a guard column IonPac AG11-HC (50 mm x 4 mm). Gradient KOH eluent generated by an eluent generation cartridge was used at a flow rate of 1.0 mL/min. The detection was performed by a Dionex suppressed conductivity detector. The quantitative analysis of external standard calibration curves was used. The linear ranges of the method for glyphosate, methyl glyphosate, hexamethylphosphoramide (HMPA), glyphosine, phosphite, phosphate, chloride and sulfate were 0.1 - 20 mg/L (r = 0.9995), 0.1 - 20 mg/L (r = 0.9993), 0.1 - 50 mg/L (r = 0.9999), 0.25 - 50 mg/L ( r = 0.9998), 0.05 - 20 mg/L (r = 0.9999), 0.2 - 50 mg/L ( r = 0.9985), 0.02 - 20 mg/L (r = 0.9999) and 0.05 - 50 mg/L (r = 0.9980), respectively. The average recoveries were 93.7% - 104.0% with the relative standard deviations less than 2.5% (n = 7), and the detection limits (S/N = 3) were 0.002 - 0.025 mg/L. The method has been applied to determine the contents of glyphosate, phosphorous by-products and inorganic anions in the mother liquor of glyphosate with satisfactory results.

Synthesis, characterisation and reactions of cationic complexes of Arylantimony (III) chlorides ArnSbCl3-n with perchlorate and tetrafluoroborate anions

Several hitherto unreported cationic complexes of the general formula [Ar2SbL][Y] and [ArSbL2][Y]2 [ Where, Ar = C6H5, L = α-Picoline, Pyridine, Ph3AsO, hexamethyl phosphoramide (HMPA), thiourea (TU) and Y = ClO4− BF4− ] have been synthesized and characterized by solid state IR, 1H NMR, elemental analysis, conductance and molecular weight measurements. The physico-chemical data, cations [Ar2SbL]+1 and[ArSbL2]+2 are assigned a pyramidal structure.DOI: http://dx.doi.org/10.3126/ijasbt.v1i2.8204 Int J Appl Sci Biotechnol, Vol. 1(2): 42-49

Interaction of Hexamethylphosphoric Triamide with m-dinitrobenzenes

Heating of 1-X-3,5-dinitrobenzenes (X is an electron-withdrawing group) in hexamethylphosphoric triamide affords the corresponding 1-X-3-dimethylamino-5-nitrobenzenes.

ChemInform Abstract: Synthesis of New Stable Phosphorus Ylides and 1,4‐Diionic Organophosphorus Compound from a Reaction Between Hexamethyl Phosphorous Triamide and Dimethyl Acetylenedicarboxylate in the Presence of CH‐Acids.

A simple and efficient one-pot three-component reaction between hexamethyl phosphorous triamide and dimethyl acetylenedicarboxylate (DMAD) in the presence of CH-acids, such as acetylacetone, 1,3-indandione, dibenzoylmethane, anthrone, and N,N-dimethylbarbituric acid, has been studied. In all cases, new and stable phosphorus ylides are obtained in excellent yields. These stable ylides exist in solution as a mixture of two geometrical isomers as a result of restricted rotation around the carbon–carbon partial double bond, resulting from conjugation of the ylide moiety with the adjacent carbonyl group. From the reaction of N,N-dimethylbarbituric acid with DMAD in the presence of hexamethyl phosphorous triamide, a 1,4-diionic organophosphorus compound is obtained. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 24:84–89, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21067

Effect of solvent power on PVDF membrane polymorphism during phase inversion

Polyvinylidene fluoride (PVDF) membranes were prepared via the phase inversion method. The focus of this paper was put on the effects of four specific solvents with different solubility power including hexamethylphosphoramide (HMPA), trimethylphosphate (TMP), N,N-dimethylformamide (DMF) and triethylphosphate (TEP) on membrane polymorphism. Polymorphism of PVDF membranes was analyzed by wide-angle X-ray diffraction (WAXD), Fourier transform infrared spectroscopy (FTIR), Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) respectively. All results revealed that the dissolution of PVDF in different solvents had a great influence on the membrane crystalline phase. The well dissolved PVDF solution tended to form α phase during phase inversion process while the poorly dissolved PVDF solution favored the formation of β phase. Furthermore, a soft coagulation bath was used during the phase inversion process to enhance the filtration permeability of the PVDF membranes. The fouling resistance to protein and mechanical properties of the membranes were also investigated.